Phyto-oestrogens and bone health

Proceedings of the Nutrition Society

Volumn 67, Issue 2, 2008, Pages 184-195

  Coxam, Véronique ^a  

^a INRA and University of Auvergne   (France)

Author keywords

Osteoporosis; Phyto oestrogens; Post menopausal women

Indexed keywords

ESTRADIOL; GENISTEIN; ISOFLAVONE DERIVATIVE; NOVASOY; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PHYTOESTROGEN; UNCLASSIFIED DRUG;

ADOLESCENT HEALTH; BONE DENSITY; BONE MASS; BONE TURNOVER; CLINICAL TRIAL; CONFERENCE PAPER; DIET THERAPY; DIETARY INTAKE; ESTROGEN DEFICIENCY; FOOD INTAKE; FRACTURE; HORMONE SUBSTITUTION; HUMAN; MENOPAUSE; MORBIDITY; NONHUMAN; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PATHOGENESIS; POSTMENOPAUSE; RISK ASSESSMENT; SOYBEAN; WOMEN'S HEALTH;

ANIMALS; BONE AND BONES; EVIDENCE-BASED MEDICINE; FEMALE; HUMANS; ISOFLAVONES; MODELS, ANIMAL; OSTEOPOROSIS, POSTMENOPAUSAL; PHYTOESTROGENS; SOYBEANS; TREATMENT OUTCOME;

ANIMALIA;

EID: 42149149279     PISSN: 00296651     EISSN: 14752719     Source Type: Journal    
DOI: 10.1017/S0029665108007027     Document Type: Conference Paper

References (104)

1. Cooper C, Campion G & Melton LJ (1992) Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2, 285-289.
2. Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115, 3318-3325.
3. Albright F & Reifenstein EC (1948) Metabolic bone disease; osteoporosis. The Parathyroid Glands and Metabolic Bone Disease, pp. 145-204 [F Albright and EC Reifenstein, editors]. Baltimore, MD: Williams & Wilkins.
4. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21, 115-137.
5. Gallagher JC (2001) Role of estrogens in the management of postmenopausal bone loss. Rheum Dis Clin North Am 27, 143-162.
6. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B & Vittinghoff E (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280, 605-613.
7. Rossouw JE, Anderson GL, Prentice RL et al. (2002) Women's health initiative. Risks and benefits of estrogen plus progestin in healthy post menopausal women. JAMA 288, 321-333.
8. Beral V, Million Women Study Collaborators, Bull D, Green J & Reeves G (2007) Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 369, 1703-1710.
9. Moggs JG & Orphanides G (2004) The role of chromatin in molecular mechanisms of toxicity. Toxicol Sci 80, 218-224.
10. Axelson M, Sjovall J, Gustafsson BE & Setchell KD (1982) Origin of lignans in mammals and identification of a precursor from plants. Nature 298, 659-660.
11. Miksicek RJ (1993) Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol 44, 37-43.
12. Setchell KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68, Suppl., 1333S-1346S.
13. Adlercreutz H & Mazur W (1997) Phyto-oestrogens and Western diseases. Ann Med 29, 95-120.
14. l'Agence Française de la Sécurité Sanitaires des Aliments (2005) Sécurité et Bénéfices des Phyto-estrogènes Apportés par l'Alimentation - Recommandations (The Safety and Benefits of Dietary Phyto-oestrogens - Recommendations). Maisons-Alfort, France: AFSSA.
15. Balk E, Chung M, Chew P et al. (2005) Effects of Soy on Health Outcomes. Evidence Report/Technology Assessment no. 126. AHRQ Publication 05-E024-2. Rockville, MD: AHRQ.
16. Brynin R (2002) Soy and its isoflavones: a review of their effects on bone density. Alt Med Rev 7, 317-327.
17. Branca F & Lorenzetti S (2005) Health effects of phytoestrogens. Forum Nutr 57, 100-111.
18. Ososki AL & Kennelly EJ (2003) Phytoestrogens: a review of the present state of research. Phytother Res 17, 845-869.
19. Ise R, Han D, Takahashi Y, Terasaka S, Inoue A, Tanji M & Kiyama R (2005) Expression profiling of the estrogen responsive genes in response to phytoestrogens using a customized DNA microarray. FEBS Lett 579, 1732-1740.
20. Moggs JG, Ashby J, Tinwell H, Lim FL, Moore DJ, Kimber I & Orphanides G (2004) The need to decide if all estrogens are intrinsically similar. Environ Health Perspect 112, 1137-1142.
21. Coxam V (2003) Prevention of osteopenia by phytooestrogens: animal studies. Br J Nutr 89, Suppl., S75-S85.
22. Adlercreutz H, Yamada T, Wähälä K & Watanabe S (1999) Maternal and neonatal phytoestrogens in Japanese women during birth. Am J Obstet Gynecol 180, 737-743.
23. Whitten PL & Patisaul HB (2001) Cross-species and interassay comparisons of phytoestrogen action. Environ Health Perspect 109, Suppl. 1, 5-20.
24. Coxam V & Gerber M (2005) Effet des phytoestrogènes sur l'ostéoporose. In Sécurité et Bénéfices des Phytoestrogè nes Apportés par l'Alimentation - Recommandations (The Safety and Benefits of Dietary Phyto-oestrogens - Recommendations), pp. 221-249. Maisons-Alfort, France: AFSSA.
25. Jones G, Dwyer T, Hynes K, Dalais FS, Parameswaran V & Greenaway TM (2003) A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males. Eur J Clin Nutr 57, 324-327.
26. Ho SC, Guldan GS, Woo J, Yu R, Tse MM, Sham A & Cheng J (2005) A prospective study of the effects of 1-year calcium-fortified soy milk supplementation on dietary calcium intake and bone health in Chinese adolescent girls aged 14 to 16. Osteoporos Int 16, 1907-1916.
27. Anderson JJ, Chen X, Boass A, Symons M, Kohlmeier M, Renner JB & Garner SC (2002) Soy isoflavones: no effects on bone mineral content and bone mineral density in healthy, menstruating young adult women after one year. J Am Coll Nutr 21, 388-393.
28. Spence LA, Lipscomb ER, Cadogan J, Martin B, Wastney ME, Peacock M & Weaver CM (2005) The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study. Am J Clin Nutr 81, 916-922.
29. Roughead ZK, Hunt JR, Johnson LK, Badger TM & Lykken GI (2005) Controlled substitution of soy protein for meat protein: effects on calcium retention, bone, and cardiovascular health indices in postmenopausal women. J Clin Endocrinol Metab 90, 181-189.
30. Messina M, Ho S & Alekel DL (2004) Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data. Curr Opin Clin Nutr Metab Care 7, 649-658.
31. Cassidy A, Albertazzi P, Lise Nielsen I et al. (2006) Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. Proc Nutr Soc 65, 76-92.
32. Weaver CM & Cheong JM (2005) Soy isoflavones and bone health: the relationship is still unclear. J Nutr 135, 1243-1247.
33. Reinwald S & Weaver CM (2006) Soy isoflavones and bone health: a double-edged sword? J Nat Prod 69, 450-459.
34. Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT & Zheng W (2005) Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med 165, 1890-1895.
35. Setchell KD, Brown NM & Lydeking-Olsen E (2002) The clinical importance of the metabolite equol - a clue to the effectiveness of soy and its isoflavones. J Nutr 132, 3577-3584.
36. Axelson M, Kirk DN, Farrant RD, Cooley G, Lawson AM & Setchell KD (1982) The identification of the weak oestrogen equol [7-hydroxy-3-(4′- hydroxyphenyl)chroman] in human urine. Biochem J 201, 353-357.
37. Possemiers S, Bolca S, Eeckhaut E, Depypere H & Verstraete W (2007) Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol Ecol 61, 372-383.
38. Niculescu MD, Pop EA, Fischer LM & Zeisel SH (2006) Dietary isoflavones differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol as compared with those who do not. J Nutr Biochem 18, 380-390.
39. Lydeking-Olsen E, Jensen JBE, Setchell KDR, Damhus M & Jensen TH (2002) Isoflavone-rich soymilk prevents bone-loss in the lumbar spine of postmenopausal women. A 2 year study. J Nutr 132, 581SAbstr.
40. Wu J, Oka J, Higuchi M et al. (2006) Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 55, 423-433.
41. Frankenfeld CL, McTiernan A, Thomas WK, LaCroix K, McVarish L, Holt VL, Schwartz SM & Lampe JW (2006) Postmenopausal bone mineral density in relation to soy isoflavone-metabolizing phenotypes. Maturitas 53, 315-324.
42. Fujioka M, Uehara M, Wu J, Adlercreutz H, Suzuki K, Kanazawa K, Takeda K, Yamada K & Ishimi Y (2004) Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice. J Nutr 134, 2623-2627.
43. Mathey J, Mardon J, Fokialakis N et al. (2007) Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats, the case for equol. Osteoporosis Int 18, 671-679.
44. Devareddy L, Khalil DA, Korlagunta K, Hooshmand S, Bellmer DD & Arjmandi BH (2006) The effects of fructo-oligosaccharides in combination with soy protein on bone in osteopenic ovariectomized rats. Menopause 13, 692-699.
45. Ten Bolscher M, Netelenbos JC, Barto R, Van Buuren LM & Van der Vijgh WJ (1999) Estrogen regulation of intestinal calcium absorption in the intact and ovariectomized adult rat. J Bone Miner Res 14, 1197-1202.
46. Omi N, Aoi S, Murata K & Ezawa I (1994) Evaluation of the effect of soybean milk and soybean milk peptide on bone metabolism in the rat model with ovariectomized osteoporosis. J Nutr Sci Vitaminol 40, 201-211.
47. Cotter AA & Cashman KD (2005) The effect of two dietary and a synthetic phytoestrogen on transepithelial calcium transport in human intestinal-like Caco-2 cells. Eur J Nutr 44, 72-78.
48. Pie JE, Park JH, Park YH, Ryu YM, Kim KN, Suh SW, Becker KG, Cho-Chung YS & Kim MK (2006) Effect of genistein on the expression of bone metabolism genes in ovariectomized mice using a cDNA microarray. J Nutr Biochem 17, 157-164.
49. Rickard DJ, Monroe DG, Ruesink TJ, Khosla S, Riggs BL & Spelsberg TC (2003) Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through oestrogen receptors alpha and beta. J Cell Biochem 89, 633-646.
50. Adlercreutz H (1998) Evolution, nutrition, intestinal microflora, and prevention of cancer: a hypothesis. Proc Soc Exp Biol Med 217, 241-246.
51. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B & Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with oestrogen receptor beta. Endocrinology 139, 4252-4263.
52. De Wilde A, Lieberherr M, Colin C & Pointillart A (2004) A low dose of daidzein acts as an ERbeta-selective agonist in trabecular osteoblasts of young female piglets. J Cell Physiol 200, 253-262.
53. de Wilde A, Heberden C, Chaumaz G, Bordat C & Lieberherr M (2006) Signaling networks from Gbeta1 subunit to transcription factors and actin remodeling via a membrane-located ERbeta-related protein in the rapid action of daidzein in osteoblasts. J Cell Physiol 209, 786-801.
54. Kanno S, Hirano S & Kayama F (2004) Effects of the phytoestrogen coumestrol on RANK-ligand-induced differentiation of osteoclasts. Toxicology 203, 211-220.
55. Jia TL, Wang HZ, Xie LP, Wang XY & Zhang RQ (2003) Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production. Biochem Pharmacol 65, 709-715.
56. Ge Y, Chen D, Xie L & Zhang R (2006) Enhancing effect of daidzein on the differentiation and mineralization in mouse osteoblast-like MC3T3-E1 cells. Yakugaku Zasshi 126, 651-656.
57. Gao YH & Yamaguchi M (2000) Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5, 261-267.
58. Sliwinski L, Folwarczna J, Janiec W, Grynkiewicz G & Kuzyk K (2005) Differential effects of genistein, estradiol and raloxifene on rat osteoclasts in vitro. Pharmacol Rep 57, 352-359.
59. Williams JP, Jordan SE, Barnes S & Blair HC (1998) Tyrosine kinase inhibitor effects on avian osteoclastic acid transport. Am J Clin Nutr 68, Suppl., 1369S-1374S.
60. García Palacios V, Robinson LJ, Borysenko CW, Lehmann T, Kalla SE & Blair HC (2005) Negative regulation of RANKL-induced osteoclastic differentiation in RAW264.7 cells by estrogen and phytoestrogens. J Biol Chem 280, 13720-13727.
61. Chen XW, Garner SC & Anderson JJ (2002) Isoflavones regulate interleukin-6 and osteoprotegerin synthesis during osteoblast cell differentiation via an estrogen-receptor-dependent pathway. Biochem Biophys Res Commun 295, 417-422.
62. Dang Z & Lowik CW (2004) The balance between concurrent activation of ERs and PPARs determines daidzein-induced osteogenesis and adipogenesis. J Bone Miner Res 19, 853-861.
63. Dang ZC & Lowik C (2005) Dose-dependent effects of phytoestrogens on bone. Trends Endocrinol Metab 16, 207-213.
64. Kardinaal AFM, Morton MS, Brüggemann-Rotgans IEM & Van Beresteijn ECH (1998) Phyto-oestrogen excretion and rate of bone loss in postmenopausal women. Eur J Clin Nutr 52, 850-855.
65. Tsuchida K, Mizushima S, Toba M & Soda K (1999) Dietary soybeans intake and bone mineral density among 995 middle-aged women in Yokohama. J Epidemiol 9, 14-19.
66. Horiuchi T, Onouchi T, Takahashi M, Ito H & Orimo H (2000) Effect of soy protein on bone metabolism in postmenopausal women. Osteoporos Int 11, 721-724.
67. Mei J, Yeung SSC & Kung AWC (2001) High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 86, 5217-5221.
68. Somekawa Y, Chiguchi M, Ishibashi T & Aso T (2001) Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 97, 109-115.
69. Kim MK, Chung BC, Yu VY, Nam JH, Lee HC, Huh KB & Lim SK (2002) Relationship of urinary phyto-oestrogen excretion to BMD in postmenopausal women. Clin Endocrinol 56, 321-328.
70. Kritz-Silverstein D & Goodman-Gruen DL (2002) Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women. J Womens Health Gend Based Med 11, 69-78.
71. Greendale GA, FitzGerald G, Huang MH, Sternfeld B, Gold E, Seeman T, Sherman S & Sowers MF (2002) Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation. Am J Epidemiol 155, 746-754.
72. Nagata C, Shimizu H, Takami R, Hayashi M, Takeda N & Yasuda K (2002) Soy product and serum isoflavonoid and estradiol concentrations in relation to bone mineral density in postmenopausal Japanese women. Osteoporos Int 13, 200-204.
73. Hanna K, Wong J, Patterson C, O'Neill S & Lyons-Wall P (2004) Phytoestrogen intake, excretion and markers of bone health in Australian women. Asia Pac J Clin Nutr 13, Suppl., S74.
74. Ikeda Y, Morita A, Kajita E, Kagamimori S, Kagawa Y & Yoneshima H (2006) Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese population-based osteoporosis (JPOS) study. J Nutr 136, 1323-1328.
75. Scambia G, Mango D, Signorile PG, Angeli RA, Palena C, Bombardelli E, Morazzoni P, Riva A & Mancuso S (2000) Clinical effects of a standardised soy extract in postmenopausal women: a pilot study. Menopause 6, 233-241.
76. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR & Kurzer MS (2000) Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 85, 3043-3048.
77. Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL & Lamia CA (2000) Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double blind, randomized, placebo-controlled study. Menopause 7, 236-242.
78. Scheiber MD, Liu JH, Subbiah MTR, Rebar RW & Setchell K (2001). Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause 8, 384-392.
79. Yamori Y, Moriguchi EH, Teramoto T, Miura A, Fukui Y, Honda K, Fukui M, Nara Y, Taira K & Moriguchi Y (2002) Soybean isofavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study. J Am Coll Nutr 21, 560-563.
80. Uesugi T, Fukui Y & Yamori Y (2002) Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal Japanese women: a four-week study. J Am Coll Nutr 21, 97-102.
81. Lucas EA, Wild RD, Hammond LJ, Khalil DA, Jum S, Daggy BP, Stoecker BJ & Arjmandi BH (2002) Flaxseed improves lipid profile without altering biomarkers of bone metabolism in post-menopausal women. J Clin Endocrinol Metab 87, 1527-1532.
82. Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME & Wild RA (2003) Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 88, 1048-1054.
83. Dalais FS, Ebeling PR, Kotsopoulos D, McGrath BP & Teede HJ (2003) The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol 58, 704-709.
84. Harkness LS, Fiedler K, Sehgal AR, Oravec D & Lerner E (2004) Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health (Larchmt) 13, 1000-10007.
85. Zittermann A, Geppert J, Baier S, Zehn N, Gouni-Berthold I, Berthold HK, Reinsberg J & Stehle P (2004) Short-term effects of high soy supplementation on sex hormones, bone markers, and lipid parameters in young female adults. Eur J Nutr 43, 100-108.
86. Roudsari AH, Tahbaz F, Hossein-Nezhad A, Arjmandi B, Larijani B & Kimiagar SM (2005) Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial. Nutr J 4, 30.
87. Potter SM, Baun JA, Teng H, Stillman RJ, Shay NF & Erdman JW (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68, 1375-1379.
88. Dalais FS, Rice GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R & Strauss BJG (1998) Effects of dietary phytoestrogens in postmenopausal women. Climateric 1, 124-129.
89. Alekel DL, St Germain A, Peterson CT, Hanson KB, Stewart JW & Toda T (2000) Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72, 844-852.
90. Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML & Moreton T (2001) The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 8, 259-265.
91. Hsu CS, Shen WW, Hsueh YM & Yeh SL (2001) Soy isoflavone supplementation in postmenopausal women. J Reprod Med 42, 221-226.
92. Chiechi LM, Secreto G, D'Amore M, Fanelli M, Venturelli E, Cantatore F, Laselva G & Loizzi P (2002) Efficacy of a soy rich diet in preventing post-menopausal osteoporosis: the Menfis randomised trial. Maturitas 42, 295-300.
93. Vitolins M, Anthony M, Lenschik L, Bland DR & Burke GL (2002) Does soy protein and its isoflavones prevent bone loss in peri- and postmenopausal women? Results of a two year randomized clinical trial. J Nutr 132, 582S.
94. Morabito N, Crisafulli A, Vergara C et al. (2002) Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Min Res 17, 1904-1912.
95. Chen YM, Ho SC, Lam SSH, Ho SSS & Woo JLF (2003) Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 88, 4740-4747.
96. Gallagher JC, Satpathy R, Rafferty K & Haynatzka V (2004) The effect of soy protein isolate on bone metabolism. Menopause 11, 290-298.
97. Lydeking-Olsen E, Jensen JBE, Setchell KDR & Jensen TH (2004) Soymilk on progesterone for prevention of bone loss. A 2-year randomized, placebo-controlled trial. Eur J Nutr 43, 246-257.
98. Kreijkamp-Kaspers S, Kok L, Grobbee DE, De Haan EHF, Aleman A, Lampe JW & Van der Schouw YT (2004). Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. A randomized controlled trial. JAMA 292, 65-74.
99. Atkinson C, Compson JE, Day NE, Dowsett M & Bingham SA (2004) The effect of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 79, 326-333.
100. Arjmandi BH, Lucas EA, Khalil DA, Devareddy L, Smith BJ, McDonald J, Arquitt AB, Payton ME & Mason C (2005) One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women. Nutr J 4, 8.
101. Huang HY, Yang HP, Yang HT, Yang TC, Shieh MJ & Huang SY (2006) One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. J Nutr Biochem 17, 509-517.
102. Newton KM, LaCroix AZ, Levy L, Li SS, Qu P, Potter JD & Lampe JW (2006) Soy protein and bone mineral density in older men and women: a randomized trial. Maturitas 55, 270-277.
103. Wu J, Oka J, Tabata I et al. (2006) Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial. J Bone Miner Res 21, 780-789.
104. Ye YB, Tang XY, Verbruggen MA & Su YX (2006) Soy isoflavones attenuate bone loss in early postmenopausal Chinese women: a single-blind randomized, placebo-controlled trial. Eur J Nutr 45, 327-334.